Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “GLOBULINS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 469 records · Page 26Linked to original sources
PubMed1956

Alterations in serum globulins during the formation and resorption of amyloid in rabbits.

A marked increase of the serum beta globulins was found in rabbits developing amyloidosis as a result of prolonged treatment with ribonucleate administered by subcutaneous injections. Following cessation of treatment the beta globulin levels gradually returned to normal while the gamma globulin levels rose strikingly, the changes being accompanied by a resorption of amyloid from the spleen, and probably also from the kidneys. Electrophoretic studies provided some evidence that the increase in beta globulins which accompanied the development of amyloidosis resulted from the production of a globulin not normally present in rabbit serum. A protein or protein derivative that moved as a beta globulin when subjected to filter paper electrophoresis was excreted in substantial quantities in the urine of several amyloidotic rabbits, along with much smaller quantities of substances moving as albumin, alpha and gamma globulins. Considered as a whole, the findings indicate a causal relationship between the abnormal production of circulating beta globulins and the deposition of amyloid in rabbits treated with ribonucleate. Hence it appears that a beta globulin may be directly involved in the formation of amyloid under the conditions of the experiments here reported.

Amyloid↗
PubMed1957

Role of gamma globulins in pathogenesis of renal lesions in systemic lupus erythematosus and chronic membranous glomerulonephritis, with an observation on the lupus erythematosus cell reaction.

Utilizing the fluorescent antibody method for the histologic demonstration of localized gamma-globulins, we have made the following observations (in contradistinction to the lack of such findings in a variety of normal and pathologic, control kidneys). In systemic lupus erythematosus (a) gamma-globulins were localized in the thickened capillary walls, the "wire-loop" lesions, and the so called "hyaline thrombi" in glomeruli; (b) these sites of localization of gamma-globulins were correlated to a considerable degree with the pattern of accentuated eosinophilia of the glomeruli, as seen in hematoxylin-eosin sections, or with the pattern of PAS-positive areas in the glomeruli in sections stained with the periodic acid-Schiff reaction; (c) and gamma-globulins were localized rarely in large cytoplasmic granules in tubular epithelium and occasionally in glomerular capsular crescents, tubular protein casts, and inflammatory cells, particularly in the cytoplasm of cells identified as immature and mature plasma cells. In nephrotic glomerulonephritis (a) gamma-globulins were localized in the glomerular basement membrane and appertaining structures in chronic membranous glomerulonephritis; (b) gamma-globulins were apparently localized in the altered mesangium in chronic lobular glomerulonephritis; and (c) in the tubular protein casts, presumably representing abnormal glomerular filtrates, gamma-globulins were present in a lesser concentration and other serum proteins in a greater concentration than found in the glomeruli. In positive lupus erythematosus preparations the nuclei of leukocytes, while undergoing transformation and subsequent phagocytosis to form lupus erythematosus cells, were the sites of localization of gamma-globulin (presumably the lupus erythematosus factor) whereas in control preparations no nuclear localization of gamma-globulin occurred. These observations are discussed in relation to the pathogenesis of renal lesions in systemic lupus erythematosus, chronic membranous glomerulonephritis, and amyloidosis.

Amyloidosis↗
PubMed1962

Genetic characters of human gamma-globulins in myeloma proteins.

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human gamma-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal gamma-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal gamma-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal gamma-globulin was Gm(a+b+). This indicates that the effect of gene Gm(b) is similar in Negroes and whites, even though its relation to gene Gm(a) is different in the two races. Gm factors were found only in the 7S gamma-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S gamma-globulins, beta(2A)-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal gamma-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal gamma-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.

Bence Jones Protein↗
PubMed1964

GAMMA GLOBULIN METABOLISM IN RABBITS DURING THE ANAMNESTIC RESPONSE.

1. Gamma globulin metabolism and distribution were studied employing rabbit gamma globulin (RGG)I(131) 24 times in 13 control rabbits. Similar studies were performed before and during the ananmestic response in 4 rabbits previously sensitized with a polyvalent pneumococcal vaccine. 2. During the ananmestic response, gamma-globulin levels increased from 1.0 to 6.0 gm/100 ml, and the gamma-globulin pool increased from 0.7 to 4.7 gm/kg. There was no change in the intravascular-extravascular partition of gamma globulin. 3. Gamma globulin degradation increased from 0.06 to 0.33 gm/kg/day during the 28 days of the immunization period while gamma globulin synthesis increased even further to average 0.47 gm/kg/day. Following the attainment of elevated gamma globulin levels the fractional rate of RGG-I(131) turnover increased from 8.0 to 12.5 per cent/day. 4. No differences were noted in the metabolism of homologous or autologous gamma globulin regardless of the allotypic specificities.

Animals↗
PubMed1967

Evidence for in vivo breakdown of beta-10-globulin in hypocomplementemic glomerulonephritis.

Evidence has been obtained for the presence in vivo of alpha(2D)-globulin, a breakdown product of serum beta(1C)-globulin, in patients with acute and persistent hypocomplementemic glomerulonephritis. The protein has been identified by immunoelectrophoretic analysis, and the amounts present have been determined by direct measurement of specific antigenic determinants present on alpha(2D). beta(1A)-Globulin, another breakdown product of beta(1C)-globulin, may also be present in vivo in severely hypocomplementemic patients, but its levels are much lower than those of alpha(2D)-globulin.Alpha(2D)-globulin has been identified by immunoelectrophoretic analysis of fresh EDTA plasma from patients with hypocomplementemic nephritis as an arc in the alpha(2) region that shows a reaction of identity with the arc representing alpha(2D)-globulin produced by aged normal serum. beta(1A)-Globulin was not seen in these patterns. Measurement of specific antigenic determinants has been carried out in both fresh EDTA plasma and aged serum. In the fresh plasma, the concentration of D antigen, found on both beta(1C)- and alpha(2D)-globulins, has been related to that of B antigen, found only on beta(1C) and taken as a measure of the concentration of this protein. In the hypocomplementemic patients, the concentration of D antigen, in comparison to that of B, was greater than in the normal subjects. Similarly, in aged serum, the level of alpha(2D) was greater than would be expected from the amount of beta(1C) that had been broken down in vitro, measured by the concentration of beta(1A). Calculations indicated that the in vivo alpha(2D) level in severely hypocomplementemic patients ranged from 7.5 to 18% of that which would be found in a pool of aged normal serum in which beta(1C) is completely broken down. The levels tended to be lower in less severely hypocomplementemic patients, and none could be detected in normal plasma. Only small quantities of A and D antigens are detectable in the urine of patients with hypocomplementemic nephritis. The rate of excretion is about equal to that of the normal subject. The study indicates that the low serum levels of beta(1C)-globulin that may be present over long periods in patients with persistent hypocomplementemic glomerulonephritis can be ascribed, in part, to in vivo breakdown of this protein as a result of reaction with immune complexes. The contribution of beta(1C) deposition on immune complexes and of diminished synthesis to the depressed serum levels cannot be assessed by the present study.

Adult↗
PubMed1994

d-Limonene induced hyaline droplet nephropathy in alpha 2u-globulin transgenic mice.

d-Limonene is a hyaline droplet inducing agent and produces nephrotoxicity in male rats when the 1,2-epoxide metabolite binds to alpha 2u-globulin. Mice, which do not synthesize alpha 2u-globulin, are resistant to hyaline droplet nephropathy. In this study, the ability of d-limonene to cause hyaline droplet nephropathy in a transgenic mouse engineered to express alpha 2u-globulin was evaluated. The C57BL/6-derived mice excreted 0.4 +/- 0.1 mg alpha 2u-globulin/day, or approximately 16 mg alpha 2u-globulin/kg body wt. This represents about 30% of the amount excreted by adult male rats (11.9 +/- 1.1 mg/day or approximately 48 mg/kg). Transgenic mice excreted less mouse urinary protein (9.3 +/- 1.2 mg/day) than normal mice (15.1 +/- 1.6 mg/day). Unlike normal male rats, untreated transgenic mice did not show significant spontaneous hyaline droplet formation. Liver microsomes from naive transgenic mice oxidized d-limonene to the cis- and transisomers of the 1,2-epoxide, and following oral treatment with [14C]d-limonene reversible binding of d-limonene equivalents to renal cytosolic proteins was observed. Furthermore, with d-limonene treatment, hyaline droplets were observed in the transgenic mouse kidneys. These droplets, however, were much smaller in size than those seen in d-limonene-treated male rats. The accumulation of alpha 2u-globulin in the kidneys of transgenic mice and normal male rats before and after d-limonene treatment was analyzed by Western blotting. These results indicated that alpha 2u-globulin was present in the kidneys of the control transgenic mice, despite the lack of spontaneous hyaline droplet formation. After d-limonene treatment, approximately a three-fold increase in alpha 2u-globulin in the transgenic mouse kidney was observed, a response similar in magnitude to that seen in d-limonene-treated male rats. These results indicate that expression of alpha 2u-globulin in a species that does not normally develop hyaline droplet nephropathy is necessary and sufficient to render that species sensitive to this renal toxicity.

Alpha-Globulins↗
PubMed2000

Plasma steroid-binding globulin mediation of differences in stress reactivity in alternative male phenotypes in tree lizards, Urosaurus ornatus.

Plasma steroid-binding globulins, for example, corticosteroid-binding globulin and sex hormone-binding globulin (SHBG), have been identified in a number of vertebrates. One possible function of these proteins is to regulate the amount of steroid delivery to target tissues, as only free steroids are believed to diffuse from the circulation to target cells. Male tree lizards, Urosaurus ornatus, exhibit alternative male reproductive tactics correlated with dewlap (throat-fan) coloration. Males with orange-blue dewlaps are aggressive and territorial, whereas males with orange dewlaps are less aggressive and employ a satellite strategy. The two types of males have similar basal levels of total plasma corticosterone and testosterone. However, testosterone levels of nonterritorial males are more sensitive than those of territorial males to negative regulation by stress-induced increases in corticosterone. We tested the hypothesis that this difference in corticosterone feedback on testosterone could be mediated, in part, by differences in binding globulin levels between the two types of males. We have identified two steroid-binding globulins in male tree lizards. The first binds androgens and estradiol with high affinity (10(-9) M) and is similar to previously described sex hormone-binding globulins. The second binds both androgens and C(21) steroids, such as progesterone and corticosterone, with higher specificity than estradiol and is best described as an androgen-glucocorticoid-binding globulin (AGBG). In both types of males, the capacity of AGBG is much higher than SHBG. In addition, AGBG capacity is significantly greater in territorial than nonterritorial males, whereas the capacity of SHBG does not differ between the two types of males. Calculations of free steroid levels based on the affinity and capacity measures suggest that although most testosterone circulates bound to binding globulins, binding capacity is high enough that binding globulins are also able to bind to other steroids such as corticosterone. Thus, differences in binding capacity between the two types of males could result in higher levels of free corticosterone in nonterritorial males than in territorial males, especially during stress-induced increases in corticosterone, and may explain why testosterone levels of nonterritorial males are more sensitive to negative feedback by corticosterone.

Aggression↗
PubMed1987

Assessment of the covalent binding potential of 2,2,4-trimethylpentane to rat alpha 2u-globulin.

Subchronic exposure of male rats to the nephrotoxin 2,2,4-trimethylpentane (TMP) causes an accumulation of protein droplets in the epithelial cells of the renal cortex. Experimental evidence suggests that these droplets contain alpha 2u-globulin, a low-molecular-weight protein found specifically in the urine of male rats. It has been proposed that aldehyde metabolites of TMP form Schiff base adducts with the lysine groups of alpha 2u-globulin and thereby inhibit renal lysosomal processing of the protein. Accordingly, the ability of TMP and its metabolites to covalently bind to alpha 2u-globulin was examined. As a model, a [14C] formaldehyde-alpha 2u-globulin Schiff base was formed. This protein adduct was stabilized by reduction with cyanoborohydride and could be identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Protein analysis by SDS-PAGE demonstrated that hepatocytes isolated from male Fischer-344 rats produced significant quantities of alpha 2u-globulin in culture, whereas hepatocytes from female rats did not. A 15-hr exposure of metabolically competent, primary cultures of male rat hepatocytes to [14C] TMP (0.1 and 0.5%, v/v), followed by reduction with cyanoborohydride, dialysis, and analysis with SDS-PAGE, revealed no evidence of radiolabeled alpha 2u-globulin. When [14C]TMP was administered to an adult male Fischer-344 rat (300 mg/kg, ig) 22, 16, and 10 hr before sacrifice, 16% of the administered radioactivity was eliminated in the urine as TMP metabolites. Analysis as above showed no TMP-derived radioactivity in fractions containing alpha 2u-globulin from liver, blood, kidney cortex, or urine. The absence of a detectable covalent interaction between TMP and alpha 2u-globulin following in vitro or in vivo exposure suggests that a TMP-alpha 2u-globulin adduct is not responsible for the excessive formation of protein droplets in the renal cortex of exposed male rats.

Alpha-Globulins↗
PubMed1992

An alternative hypothesis on the role of chemically induced protein droplet (alpha 2u-globulin) nephropathy in renal carcinogenesis.

Based on associations between the accumulation of protein droplets containing alpha 2u-globulin in proximal tubular epithelial cells and increased incidences of renal tubular neoplasms in male rats, it has been suggested that the carcinogenicity of chemicals that cause alpha 2u-globulin nephropathy is unique to animals that synthesize this protein. Chemicals that caused alpha 2u-globulin nephropathy and renal carcinogenicity in male rats have not been shown to produce renal tumors in animals that lack the capability for hepatic alpha 2u-globulin synthesis, including female rats, male NBR rats, or mice of either sex. Because humans do not synthesize alpha 2u-globulin it has been suggested that chemicals which cause renal toxicity associated with alpha 2u-globulin accumulation do not pose an increased cancer risk to humans. In this review on the association between alpha 2u-globulin nephropathy and renal carcinogenesis, it is apparent that (a) there are data inconsistent with the hypothesis linking these occurrences, (b) alternative mechanisms of renal toxicity and carcinogenicity are plausible, (c) data on quantitative dose-response correspondences between the various stages of alpha 2u-globulin nephropathy and renal carcinogenicity are limited, and (d) a greater understanding of the molecular changes occurring during renal carcinogenesis is needed before assuming that the current hypothesis is correct. Future research aimed at resolving issues raised in this paper should help determine whether or not the association between alpha 2u-globulin nephropathy and renal carcinogenesis represents a cause-and-effect relationship.

Alpha-Globulins↗
PubMed1980

[On the origin and diagnostic value of the CSF-beta-globulins (author's transl)].

208 cerebrospinal fluid samples were taken from patients having various patterns of neurological diseases. The following beta-globulins: transferrin, haemopexin, beta-1 A-globulin, beta-1 E-globulin, beta-2-glycoproteid and beta-lipoproteid were determined immunologically quantitatively in the CSF and partly quantitatively in the serum, and their behaviour was compared with that of the beta and tau fraction in CSF electrophoresis. It was found that changes in the fractions in CSF electrophoresis agreed only slightly with those of the quantitatively determined globulins, although these globulins represent 70--80% of the beta and tau fraction. Increases in the number of beta-1 A and beta-1 E-globulins are more significantly marked in intracranial haemorrhages than with other diseases. In all other respects, increases or decreases in the number of beta-globulins do not appear to be typical of any particular disease pattern determined by electrophoresis or quantitatively. Due to the linearity of the changes in case of disturbances of the CSF barrier, and also on account of the absolutely parallel behaviour of the beta-globulins, it was concluded that transferrin--contrary to the opinion held so far--is produced cerebrally in only small quantities or possibly not at all, and that the entirety of beta-globulins originate from the serum.

Adolescent↗
PubMed1961

Immunochemical studies of twenty mouse myeloma proteins: evidence for two groups of proteins similar to gamma and beta-2A globulins in man.

The serum myeloma proteins associated with 20 mouse plasma cell tumors in C(3)H or BALB/c mice that had proved transplantable were characterized by electrophoretic and immunochemical techniques. Although the myeloma proteins ranged in electrophoretic mobility from gamma to alpha globulins, they could be divided into two groups, the gamma type and the beta type myeloma globulins, on the basis of characteristic immunochemical properties. Gamma type myeloma proteins (5563, MPC-11) showed a close immunochemical relationship to normal mouse gamma globulins. Eighteen beta type mouse myeloma proteins migrated as beta or alpha globulins on zone electrophoresis. These proteins shared common antigenic features which permitted their recognition, separate from gamma myeloma proteins. The beta type myeloma proteins were shown to be related to a beta globulin component present in normal serum. Strain differences were observed for the normal beta globulin component believed to be formed in plasma cells. The proteins formed in mouse plasma cells were found to be antigenically complex. Shared antigenic determinants as well as distinctive antigenic determinants were detected when representative myeloma proteins were purified and compared by the Ouchterlony double diffusion technique. The myeloma proteins associated with each of the transplantable plasma cell tumors in mice are regarded as distinctive and characteristic products of plasma cell metabolism. The variety of myeloma globulins was similar for plasma cell tumors arising in C(3)H as well as in BALB/c mice, indicating that differences in mouse strains would not account for the differences among the myeloma globulins. These differences, however, may be due to differences among the normal plasma cells from which the malignant cells are derived. If this is so, the variety of myeloma globulins reflect the variety of plasma cells present normally.

Animals↗
PubMed1992

Low density lipoprotein receptor activity is modulated by soybean globulins in cell culture.

The effects of major storage globulins from soybean on cholesterol homeostasis were investigated in vitro and in vivo systems. The low density lipoprotein (LDL) uptake and degradation was studied both in human skin fibroblasts (HSF) and in a human hepatoma cell line (Hep G2). In Hep G2 cells a dose-dependent increase of both uptake and degradation of 125I-LDL was induced by the 7S globulin, whereas the 11S globulin exerted a lesser effect that was not dose-related. In HSF cells the 11S globulin increased the uptake of 125I-LDL to a greater extent than did 7S globulin; in this cell line, LDL degradation was not stimulated by either of the globulins. Rats fed a casein-cholesterol diet were treated daily with the 11S or 7S globulins for 2 wk. The administration of soybean globulins significantly reduced cholesterolemia (-35 and -34% with 7S and 11S globulins, respectively, vs. controls). Liver membrane preparations from the casein-cholesterol-fed rats showed a nonsignificant increase in the maximal binding of labeled cholesterol-rich lipoprotein fraction (beta-VLDL) to high affinity receptors.

Animals↗
PubMed1986

Suppression of testosterone-estradiol binding globulin by medroxyprogesterone acetate in polycystic ovary syndrome.

Serum androgen binding capacity is decreased in hirsute women and normal women receiving medroxyprogesterone acetate. A sensitive radioimmunoassay was used to measure the main androgen binding protein, testosterone-estradiol-binding globulin, in 13 patients with hirsutism and the polycystic ovary syndrome. Testosterone-estradiol-binding globulin concentrations were determined before, during, and after treatment with medroxyprogesterone acetate. Testosterone-estradiol-binding globulin was lower in untreated polycystic ovary syndrome patients than in normal controls (21.9 +/- 3.7 versus 64 +/- 4 nmol/L, P less than .01). Administration of medroxyprogesterone acetate (400 mg intramuscularly every 15 days for nine months) to polycystic ovary syndrome patients caused a decrease of serum testosterone and further lowering of testosterone-estradiol-binding globulin (7.6 +/- 1.9 nmol/L, P less than .01). In two patients the concentration of testosterone-estradiol-binding globulin reached values as low as 0.9 and 0.8 nmol/L, approximately 1/60 and 1/70 of the normal level. Testosterone-estradiol-binding globulin returned to basal levels (15.1 +/- 1.3 nmol/L) between one and two years after discontinuation of medroxyprogesterone acetate. Corticosteroid binding globulin levels were normal in polycystic ovary syndrome and did not change with medroxyprogesterone acetate. It was concluded that: medroxyprogesterone acetate causes marked lowering of plasma testosterone-estradiol-binding globulin; the effect is not mediated by sex hormone levels; and the decrease in testosterone-estradiol-binding globulin offsets, at least partially, the beneficial action of medroxyprogesterone acetate.

Female↗
PubMed2006

Structure of 8Salpha globulin, the major seed storage protein of mung bean.

The 8S globulins of mung bean [Vigna radiata (L.) Wilczek] are vicilin-type seed storage globulins which consist of three isoforms: 8Salpha, 8Salpha' and 8Sbeta. The three isoforms have high sequence identities with each other (around 90%). The structure of 8Salpha globulin has been determined for the first time by X-ray crystallographic analysis and refined at 2.65 A resolution with a final R factor of 19.6% for 10-2.65 A resolution data. The refined 8Salpha globulin structure consisted of 366 of the 423 amino-acid residues (one subunit of the biological trimer). With the exception of several disordered regions, the overall 8Salpha globulin structure closely resembled those of other seed storage 7S globulins. The 8Salpha globulin exhibited the highest degree of sequence identity (68%) and structural similarity (a root-mean-square deviation of 0.6 A) with soybean beta-conglycinin beta (7S globulin). Their surface hydrophobicities are also similar to each other, although their solubilities differ under alkaline conditions at low ionic strength. This difference seems to be a consequence of charge-charge interactions and not hydrophobic interactions of the surfaces, based on a comparison of the electrostatic potentials of the molecular surfaces. The thermal stability of 8Salpha globulin is lower than that of soybean beta-conglycinin beta. This correlates with the cavity size derived from the crystal structure, although other structural features also have a small effect on the protein's thermal stability.

Amino Acid Sequence↗
PubMed1969

The break-down of 131-I-gamma-globulin in the digestive tract of the new-born pig.

1. The intestinal absorption of [(131)I]porcine and bovine serum gamma-globulin after oral administration has been investigated in conscious pigs less than 20 hr old. Absorption was measured by the concentration of (131)I in venous blood during the 6 hr after feeding and also by the distribution of (131)I between homogenates of the alimentary tract and the rest of the animal at the end of the experiment.2. The concentration of (131)I in the blood was always low after feeding [(131)I]gamma-globulin, although a large proportion of the isotope fed was found to have left the alimentary tract. This indicated that much of the [(131)I]-gamma-globulin had been hydrolysed into fragments of low mol.wt. which were not retained in the plasma. There were no significant differences between results obtained with homologous and heterologous gamma-globulin.3. Examination by gel-filtration confirmed that, after feeding [(131)I]-serum gamma-globulin, much of the (131)I in the plasma was associated with material of mol.wt. less than 12,400 and demonstrated that the break-down of bovine gamma-globulin was comparable with that of homologous gamma-globulin.4. Comparison of the absorption of [(131)I]serum gamma-globulin from colostrum with that from a chloride solution with a similar Na(+) and K(+) concentration showed that, although the blood concentration remained low, colostrum reduced the hydrolysis of the labelled protein.5. This effect of colostrum could be simulated by the addition to the chloride solution of either the synthetic trypsin inhibitor Trasylol or a higher concentration of unlabelled protein.6. Gel-filtration of samples of the contents of the stomach, duodenum and terminal ileum after feeding [(131)I]serum gamma-globulin showed that proteolysis occurred at all these sites.

Animals↗
PubMed1985

Hormone binding globulins and anticonvulsant therapy.

Serum sex hormone binding globulin, thyroxine binding globulin, cortisol binding globulin and vitamin D binding globulin, together with total levels of the appropriate bound hormones, were determined in 21 epileptic subjects who had been stabilised by long-term anticonvulsant therapy. Serum sex hormone binding globulin capacity was higher in these patients than in appropriate control groups (men p less than 0.05; women p less than 0.01), and values correlated with serum phenytoin levels in the female subjects (p less than 0.01). Thyroxine binding globulin levels were unaffected by anticonvulsants, but significant reductions in serum thyroxine (men p less than 0.05; women p less than 0.001) and triiodothyronine (men p less than 0.05; women p less than 0.01) were observed. Cortisol binding globulin capacity was appreciably elevated in patients of either sex (p less than 0.001), and in the women this was accompanied by a reduction in serum cortisol (p less than 0.001) and a significant correlation with the serum phenytoin concentration (p less than 0.01). Neither vitamin D binding globulin capacity nor serum 25-hydroxycholecalciferol levels were influenced by anticonvulsants in this study. It is concluded that anticonvulsant drug therapy causes widespread alterations in the normal homeostasis between hormones and their serum binding globulins. Such alterations may well have clinical significance.

Adult↗
PubMed2006

Bound homocysteine, cysteine, and cysteinylglycine distribution between albumin and globulins.

BACKGROUND: Major portions of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (CysGly), and glutathione in serum are covalently bound to proteins via disulfides. Albumin has been considered the dominant binding protein. METHODS: Pooled serum and plasma from healthy adults were fractionated into albumin and globulins by affinity columns. Content of Hcy, Cys, CysGly, and glutathione was determined for serum and plasma fractions and purified proteins by an HPLC method before and after incubation with excess CysGly, Hcy, or glutathione RESULTS: Of protein-bound amino acids in pooled serum, 12% of Hcy, 21% of Cys, and 33% of CysGly were bound to globulins, with the remainder bound to albumin. Slightly higher proportions were bound to globulins in pooled plasma. Globulins had approximately 16% of total exchangeable disulfide and thiol groups in serum based on results of loading with CysGly. These results agree with expected abundance of unpaired Cys residues in globulins relative to albumin. Significant amounts of disulfide-linked amino acids were detected for HDL and alpha1-acid glycoprotein but not for transferrin. Exchange of disulfide-linked amino acids on exposure to excess Hcy or glutathione was much faster for albumin than for alpha1-acid glycoprotein. CONCLUSIONS: Approximately 10%-30%, of protein-bound Hcy, Cys, and CysGly are disulfide-linked to globulins. Amino acids disulfide-linked to albumin are rapidly exchangeable, while exchange of disulfide-linked amino acids from globulins, such as alpha1-acid glycoprotein, is much slower. Consequently, the pools of Hcy, Cys, and CysGly bound to albumin and globulin may represent kinetically and functionally distinct pools. Plasma concentrations of total Hcy and Cys, which are dominated by albumin-bound pools, may not reflect the abundance of functionally significant modifications of globulins.

Adult↗
PubMed2001

Gamma globulin levels predict type 2 diabetes in the Pima Indian population.

It has been proposed that inflammation or infection may contribute to the development of type 2 diabetes. We examined whether serum gamma globulin, a nonspecific measure of the humoral immune system, predicted changes in glucose tolerance in 2,530 members of the Pima Indian population, a group with a marked predisposition to type 2 diabetes. Cross-sectionally, gamma globulin was positively related to age (r = 0.08, P < 0.0005), BMI (r = 0.09; P < 0.0001), and female sex (P < 0.0001). Gamma globulin concentrations were familial, being positively correlated among siblings (r = 0.23; P < 0.0001) and between parents and their children (mother/child: r = 0.17, P < 0.0001; father/child: r = 0.25, P < 0.0001). Gamma globulin concentrations were higher with greater degrees of American Indian heritage (P < 0.004, with adjustment for age, sex, and BMI) and in the presence of a family history of type 2 diabetes (P < 0.04). Higher gamma globulin levels predicted risk of diabetes. In univariate analysis, a 1 SD difference in gamma globulin was associated with a 20% higher incidence of diabetes in those who were normal glucose tolerant at baseline (hazard rate ratio 1.20 [CI 1.11-1.30]; P < 0.0001) and remained as a significant predictor of diabetes, even when controlled for effects of sex, BMI, and 2-h glucose as additional predictors (hazard rate ratio for 1 SD difference in gamma globulin, 1.14 [1.05-1.24]; P = 0.002). Gamma globulin was also associated in univariate analysis with later development of impaired glucose tolerance (IGT) (hazard rate ratio 1.15 [1.07-1.23]; P < 0.0001), but not with the transition from IGT to diabetes (hazard rate ratio 1.04 [0.90-1.20]; P = 0.6). Thus, gamma globulin levels predict increased risk of diabetes in the Pima population. We suggest that immune function or activation may play a role in the development of type 2 diabetes.

Adult↗